Dual roles for cholesterol in mammalian cells

Fang Xu, Scott D. Rychnovsky, Jitendra D. Belani, Helen H. Hobbs, Jonathan C. Cohen, Robert B. Rawson

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

Abstract

The structural features of sterols required to support mammalian cell growth have not been fully defined. Here, we use mutant CHO cells that synthesize only small amounts of cholesterol to test the capacity of various sterols to support growth. Sterols with minor modifications of the side chain (e.g., campesterol, β-sitosterol, and desmosterol) supported long-term growth of mutant cells, but sterols with more complex modifications of the side chain, the sterol nucleus, or the 3-hydroxy group did not. After 60 days in culture, the exogenous sterol comprised >90% of cellular sterols. Inactivation of residual endogenous synthesis with the squalene epoxidase inhibitor NB-598 prevented growth in β-sitosterol and greatly reduced growth in campesterol. Growth of cells cultured in β-sitosterol and NB-598 was restored by adding small amounts of cholesterol to the medium. Surprisingly, enantiomeric cholesterol also supported cell growth, even in the presence of NB-598. Thus, sterols fulfill two roles in mammalian cells: (i) a bulk membrane requirement in which phytosterols can substitute for cholesterol and (ii) other processes that specifically require small amounts of cholesterol but are not enantioselective.

Original languageEnglish (US)
Pages (from-to)14551-14556
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number41
DOIs
StatePublished - Oct 11 2005

Keywords

  • NB-598
  • Phytosterols
  • ent-cholesterol

ASJC Scopus subject areas

  • General

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